This Month in the Journal

ROLE OF THE PONS IN BREATHING

More than 70 years have elapsed since Thomas Lumsden’s classic studies of the influence of the pons on respiration, yet this topic remains unsettled and controversial. Do pontine mechanisms play a central role in the neurogenesis of breathing or is their action a subordinate and nonessential modulation of the output of an exclusively medullary respiratory rhythm generator? Jodkowski et al. (p. 377) contribute new information to this debate with their report that microinjections of glutamate at a site in the ventrolateral pons cause reversible prolongation of neural expiration in anesthetized vagotomized rats. The injection site is anatomically distinct from the pneumotaxic region in the dorsolateral pontine tegmentum. The paper is discussed in an Invited Editorial by St. John (p. 375).

LONG-TERM FACILITATION OF UPPER AIRWAY MUSCLE ACTIVITIES

Regulation of breathing proceeds on many different time scales. Carotid sinus nerve stimulation in vagotomized cats leads to increased ventilation for up to 90 min after the stimulation has ended, a phenomenon termed “long-term facilitation” (LTF). Mateika and Fregosi (p. 419) demonstrate that LTF occurs in the activities of upper airway muscles and that LTF is much greater in vagotomized cats than in those with intact vagi. They suggest that in humans, who have relatively weak vagal reflex responses to lung inflation, LTF may act correctively to improve upper airway patency after periods of chemostimulation by episodes of obstructive sleep apnea.

CLENBUTEROL AND EXERCISE FOR TREATMENT OF MUSCULAR DYSTROPHY?

Clenbuterol, a β2-agonist, has potent anabolic properties in skeletal muscle and is thus an attractive candidate drug for use in the prevention of muscle atrophy in dystrophin-deficient muscular dystrophy. A potential drawback, however, is that clenbuterol promotes a fiber type transition from slow-twitch to fast-twitch fibers, which are preferentially affected by the dystrophic process. Hayes and Williams (p. 435) report that a low-intensity exercise program in dystrophic mice prevents the clenbuterol-induced shift in fiber type while preserving the strength-increasing effects of the drug. This result has likely clinical applicability in the treatment of patients with some types of muscular dystrophy.

POTENTIALS EVOKED BY PHRENIC NERVE STIMULATION

Respiratory sensation undoubtedly involves cortical processing of afferent activity. Straus et al. (p. 480) recorded scalp and cervical spinal potentials evoked by transcutaneous stimulation of a phrenic nerve in human subjects. Consistent negative potentials were recorded over the second cervical segment at ∼7 ms and on the scalp at ∼13 ms. The cervical potential may represent the ascending afferent volley. The scalp potential could have several causes, but the authors hypothesize that it represents an afferent projection to the anterior part of the cingulate gyrus—part of the limbic system. The significance of these potentials for respiratory sensation remains to be established.

TRANSPLEURAL INERT-GAS TRANSFER IN ISOLATED LUNGS

Li et al. (p. 545) studied the loss of inert gases from the blood across the pleura of an isolated, ventilated, and perfused rabbit lung placed within a box with flowing gas surrounding the lung. A single-compartment model showed transpleural gas flux from the blood depended on four dimensionless ratios: the perfusate-to-air partition coefficient, the alveolar ventilation-to-perfusion ratio, the ratio of pleural diffusing capacity to ventilation conductance, and the box ventilation-to-alveolar ventilation ratio. The concentrations of six inert gases were measured in pulmonary arterial blood, venous blood, exhaled gas, and box gas. The experimental data were adequately described by the single-compartment model.

EFFECT OF RUNNING ON INTESTINAL PERMEABILITY

Gastrointestinal disorders are commonly reported among long-distance runners. Although alterations in small intestinal permeability have been observed, the actual mechanisms responsible are unclear. Pals and co-workers (p. 571) evaluated the effect of running on small intestinal permeability, evident by an increase in the urinary excretion ratio of lactulose to rhamnose, and an index of gastric damage by using sucrose as a probe. Measurements were made during rest or during and following 60 min of treadmill exercise at 40, 60, and 80% peak oxygen uptake in six healthy subjects. There was no evidence of gastric damage, as urinary recovery of sucrose was not altered. Increased small intestinal permeability was found at the highest exercise intensity, but the prevalence of gastrointestinal symptoms was small and did not correspond to increased permeability. The significance and mechanisms involved in the increased small intestinal permeability after high-intensity running merit further investigation.

EFFECT OF MUSCLE ISCHEMIA ON BAROREFLEX RESPONSES

Arterial blood pressure is closely controlled by reflexes arising from the carotid sinus baroreceptors. This mechanism can be quantified in human subjects by applying pulsatile positive and negative pressures to the neck and plotting mean arterial pressure as a function of carotid sinus transmural pressure. The negative slope of such a plot is a measure of baroreflex sensitivity. Afferents from ischemic muscle also elevate blood pressure—the muscle chemoreflex. Papelier et al. (p. 577) examined the interaction of these two reflex systems by assessing the influence of postexercise muscle ischemia on the baroreflex response curve in seven healthy subjects. Bicycle exercise shifted the curve upward and rightward, and postexercise leg ischemia, induced by inflation of thigh cuffs, further elevated mean arterial pressure. The summation of effects was alinear in that baroreflex sensitivity was enhanced at low carotid sinus pressures but reduced at high carotid sinus pressures.

INDUCED PERIODIC BREATHING IN LAMBS

Periodic breathing in association with hypoxia is common in human adults and infants, especially during sleep, but is relatively uncommon in neonates of other species. Canet et al. (p. 607) used an extracorporeal membrane lung to manipulate arterialPCO2 andPO2 in awake 2- and 10-day-old lambs. Substantial reductions in both PCO2and PO2 consistently induced periodic breathing in the 10-day-old lambs but only rarely in the 2-day old animals, which exhibited low chemoresponsiveness. This result is interpreted to indicate that the induction of periodic breathing by hypoxia and hypocapnia requires relatively mature ventilatory responses to chemical stimuli.

EXERCISE TRAINING PROMOTES BLOOD CLOTTING AND FIBRINOLYSIS

Blood coagulation and fibrionolysis constitute two physiological opponents in hemostasis and thrombus formation. Van den Burg et al. (p. 613) report that previously sedentary subjects engaging in 12 wk of submaximal exercise training increased factor VIII coagulant activity, reflected in a decrease in partial thromboplastin time during maximal exercise. Fibrinolytic potential was also enhanced. The results were complicated by an opposite effect on fibrinolysis in nonexercising control subjects studied over the same period (February–June). Thus training promotes both coagulation and fibrinolytic potential during exercise and may counteract unfavorable seasonal effects on fibrinolysis.

REGIONAL HETEROGENEITY OF PULMONARY BLOOD FLOW

Pulmonary perfusion heterogeneity is an important determinant of the gas- exchange function of the lungs. The role of gravity in determining the regional distribution of perfusion in the lungs is well known, but recently there has been considerable interest in observations of nongravity-dependent heterogeneity (see Invited Editorial by J. M. B. Hughes, J. Appl. Physiol. 81: 1049–1050, 1996). Walther et al. (p. 678) revisited this problem in the sheep by measuring the three-dimensional flow distribution using the fluorescent-microsphere method. The researchers found that, in this species, there is a systematic decrease in regional flow with distance from the hilum that accounts for ∼34% of the flow variability in the lungs. They did not detect a vertical gradient attributable to effects of gravity.